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Biosensors for Health Applications
Cibele Marli Cação Paiva Gouvêa
Universidade Federal de Alfenas Brazil 1. Introduction
The ability to assess health status, disease onset and progression, and monitor treatment outcome through a non-invasive method is the main aim to be achieved in health care promotion and delivery and research. There are three prerequisites to reach this goal: specific biomarkers that indicates a healthy or diseased state; a non-invasive approach to detect and monitor the biomarkers; and the technologies to discriminate the biomarkers. The early disease diagnosis is crucial for patient survival and successful prognosis of the disease, so that sensitive and specific methods are required for that. Among the numerous mankind diseases, three of them are relevant because of their worldwide incidence, prevalence, morbidity and mortality, namely diabetes, cardiovascular disease and cancer. In recent years, the demand has grown in the field of medical diagnostics for simple and disposable devices that also demonstrate fast response times, are user-friendly, costefficient, and are suitable for mass production. Biosensor technologies offer the potential to fulfill these criteria through an interdisciplinary combination of approaches from nanotechnology, chemistry and medical science. The emphasis of this chapter is on the recent advances on the biosensors for diabetes, cardiovascular disease and cancer detection and monitoring. An overview at biorecognition elements and transduction technology will be presented as well as the biomarkers and biosensing systems currently used to detect the onset and monitor the progression of the selected diseases. The last part will discuss some challenges and future directions on this field.

2. Biorecognition elements and transduction technology
2.1 Biorecognition elements Clinical analyses are no longer carried out exclusively in the clinical chemistry laboratory. Measurements of analytes in biological fluids are routinely performed in various locations, including hospital, by caregivers in non-hospital settings and by patients at home. Biosensors (bioanalytical sensors) for the measurement of analytes of interest in clinical chemistry are ideally suited for these new applications. These factors make biosensors very attractive compared to contemporary chromatographic and spectroscopic techniques. A biosensor can be generally defined as a device that consists of a biological recognition system and a transducer, for signal processing, to deduce and quantity a particular analyte (Hall, 1990). Biosensors provide advanced platforms for biomarker analysis with the advantages of being easy to use, rapid and robust as well as offering multianalyte testing

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cell receptors to their ligands. Substantial amounts of published work on the enzyme-based biosensors are found in the literature due to their medical applicability. 2001. Immunosensors are based on the high selectivity of the antibody–antigen reaction. The specific interaction is sensed by a transducer and measurements can be obtained directly. thermal and mass-based biosensors. Amongst various enzymes. in some cases. 1998) or the signal transduction method (electrochemical. The major limitation is the lack of specificity in differentiating among compounds of similar classes (Buerk.. since they provide information about binding of antibodies to antigens. H2O2.intechopen. however a specific biomarker is necessary. biosensors can be categorized according to the biological recognition element (enzymatic. A major advantage of enzyme-based biosensors is the ability. By acting as biocatalytic elements. 2003).72 Biosensors for Health. The first biosensor was reported by Clark and Lyons (1962) for glucose in blood measurement. The enzyme-based sensor was the first generation of biosensors and in the subsequent years a variety of biosensors for other clinically important substances were developed. Wanekaya et al. optical. commercial availability or ease of enzyme isolation and purification from different sources and also enzymes can be used in combination for detection of a target analyte (D'Orazio. rather than the hours required for visualizing results of an ELISA test www. The detection limit is satisfactory or exceeded but the enzyme stability is still a problem.. Schematic of a biosensor (Arya et al. to modify catalytic properties or substrate specificity by genetic engineering. 2000). proportionally to the glucose concentration in the sample. Therefore. DNA/RNA to complementary sequences of nucleic acids and functioning enzymatic pathways that allow the screening of gene products for metabolic functions. and alkaline phosphatase have been employed in most biosensor studies (Laschi et al. D'Orazio. 2008). O2 or by the activation/inhibition activity that can be detected easily by various transducers and correlate this species to the substrates. H+. 1. Spichiger-Keller. 2000. Environment and Biosecurity capability. 2003). The enzyme-catalyzed oxidation of glucose consumed O2 and lowered PO2 that was sensed. 2008) (Fig 1). especially considering a long period of time. DNA and whole-cell biosensors. Affinity biosensors have received considerable attention in the last years.. Wang. glucose oxidase. Fig. 2010). horseradish peroxidase. the enzymatic reaction is accompanied by the consumption or production of species such as CO2. in minutes. immuno.. NH3. 1993. They coupled the enzyme glucose oxidase to an amperometric electrode for PO2. Biomarkers are molecules that can be objectively measured and evaluated as indicators of normal or disease processes and pharmacologic responses to therapeutic intervention (Rusling et al.com .

The sensors may operate either as direct or as indirect sensors often referred to homogeneous and heterogeneous immunosensors. Hybridization can be performed either in solution or on solid supports. Whole-cell biosensors are based in the general metabolic status of bacteria. Either an antigen or antibody can be immobilized onto a surface of support in an array format (Huang et al. 1999). Conducting polymers. 2009). 1993) although intensive research effort has been directed toward the regeneration of renewable antibody surfaces. However. partly due to the antibody orientation and immobilization onto the sensor surface. ionic strength and chemical composition. This improvement has stimulated the development of DNA biosensors with a view toward rapid analysis for point-of-care diagnostics for infectious disease. a time-consuming process.. this may compromise their selectivity (Ding et al.Biosensors for Health Applications 73 (Spangler et al.. A variety of transducer methods have been feasible toward the development of biosensor www. 2002). The system can be used for repeated analysis since the nucleic acid ligands can be denatured to reverse binding and then regenerated (Ivnitski et al. carbon nanotubes. in general. Reproducibility is another concern. DNA is well suited for biosensing because the base pairing interactions between complementary sequences are both specific and robust.2 Transduction technology The interaction of the analyte with the bioreceptor is designed to produce an effect measured by the transducer. nanoparticles. usually.. Many enzymes and cofactors that co-exist in the cells give them the ability to consume and hence detect a large number of chemicals. Immunosensors are currently been used for infectious diseases diagnosis (Huang et al. temperature. only a single immunoassay can be performed (Buerk. 2004). 2001). 2. As the antibody–antigen complex is almost irreversible. need to multiply small amounts of DNA into readable quantities using the polymerase chain reaction (PCR). Chemical properties of a desired support decide the method of immobilization and the operational stability of a biosensor. Antibodies are the critical part of an immunosensor to provide sensitivity and specificity. animal or plant cells that are the recognition elements. the matrix... and even a whole cancer circulating cell can be identified (Liu et al. However. In particular. it should be resistant to a wide range of physiological pHs.. respectively. 2002). The sensing molecule.. yeasts. DNA analysis is the most recent and most promising application of biosensors to clinical chemistry. DNA biosensors employ immobilized relatively short synthetic single-stranded oligodeoxynucleotides that hybridizes to a complementary target DNA in the sample (Palecek. Whole cells can easily be manipulated and adapted to consume and degrade new substrates. fungi. 2004) and participates in a biospecific interaction with the other component. 2008). Immunosensors are inherently more versatile than enzyme-based biosensors because antibodies are more selective and specific. is hold on a solid support. The ability to co-immobilize more than one biologically active component is desirable in some cases. testing cancer and genetic disease diagnosis and measurement of drug resistance or susceptibility..intechopen. sol–gel/hydro-gels and self-assembled monolayer are common used to immobilize a variety of sensing molecules (Arya et al. considerable research is still needed to develop methods for directly targeting natural DNA present in organisms and in human blood with high detection sensitivity (Palecek. Some of the new gene chips are sensitive enough to eliminate the need for target amplification. Accurate tests for recognizing DNA sequences.com . 2008). allowing detection and quantification of an analyte of interest (Stefan et al. which converts the information into a measurable signal. 2000).

Light entering an optical device is directed through optical fibers or planar waveguides toward a sensing surface and reflected back out again. Generation of heat during a reaction can be used in a calorimetric based biosensor. which bend when a voltage is applied to the crystal. however the most common methods are electrochemical. and measuring the change in resonant frequency when the target analyte interacts with the sensing surface. revealing information about the physical events occurring at the sensing surface. Amperometry is the electrochemical technique usually applied in commercially available biosensors for clinical analyses that detect redox reactions. are the most common sensors. however. The measured optical signals often include absorbance.intechopen. This approach is well suited for enzyme/substrate reactions that cause changes in solution temperature but not for receptorligand reactions because there is no temperature change at steady-state and transient measurements are very difficult to make. Of particular interest have been direct optical transducers based on methods such as internal reflectance spectroscopy. 2010). usually a vibrating piezoelectric quartz crystal. The electrochemical assay is simple. or changes in light reflectivity. Wang. Most optical methods of transduction require a spectrophotometer to detect signal changes. The reflected light is monitored. Based on that and cost competitiveness. Calorimetric microsensors have been manufactured for detection of cholesterol in blood serum based on the enzymatically produced heat of oxidation and decomposition reactions (Caygill et al.g. optical and piezoelectric (Buerk. using a detector such as a photodiode. are based on electrochemical transducers (Meadows. amperometric (a change in the measured current at a given applied voltage). Optical transducers can be used to monitor affinity reactions and have been applied to quantitate antigenic species of interest in clinical chemistry and to study the kinetics and affinity of antigen–antibody and DNA interactions. they cannot be easily miniaturized for insertion into the bloodstream. fluorescence. field monitoring applications (e. Changes in solution temperature caused by the reaction are measured and compared to a sensor with no reaction to determine the analyte concentration.74 Biosensors for Health. reliable. www. Because a significant amount of nonspecific adsorption occurs in solutions.. 1993. Acoustic wave devices. or conductometric (a change in the ability of the sensing material to transport charge). Extremely high sensitivities are possible with these devices detecting femtogram levels of drug vapors. Mass sensors can produce a signal based on the mass of chemicals that interact with the sensing film. surface plasmon resonance and evanescent wave sensing. piezoelectric sensors have received their widest use in gas phase analyses. 1996). Electrochemical sensors measure the electrochemical changes that occur when analytes interact with a sensing surface of the detecting electrode. handheld) and miniaturization toward the fabrication of an implantable biosensor. made of piezoelectric materials. The electrochemical platform is suited for enzyme-based and DNA/RNA sensors. chemiluminescence. has a low detection limit and a wide dynamic range due to the fact that the electrochemical reactions occur at the electrode–solution interfaces. Optical biosensors are preferable for screening a large number of samples simultaneously. reported in the literature. The electrical changes can be potentiometric (a change in the measured voltage between the indicator and reference electrodes). Similarly to optical detection. more than half of the biosensors. surface plasmon resonance (to probe refractive index). piezoelectric detection requires large sophisticated instruments to monitor the signal. 2000). Collings & Caruso 1997.com . Acoustic wave sensors are operated by applying an oscillating voltage at the resonant frequency of the crystal. Environment and Biosecurity technology.

intechopen. Lasker. the inconvenience and the discomfort involved with the traditional measurement technique. kidney failure. elimination of oxygen dependency. to short periods of time. Diffusion of low-molecular-weight substances from the sample across the polyurethane sensor outer membrane results in loss of sensor sensitivity. In order to address the problem. 1997). micro-volume and low-cost approach for glucose analysis which is appropriate for rapid field tests and is also effective as an alternative to the existing methods. The glucose biosensor is the most widely used example of an electrochemical biosensor which is based on a screenprinted amperometric disposable electrode. However. including implantable sensors for measuring glucose in blood or tissue. Consequently. quantitation of the glucose content is of extreme importance. sensitive. www. high blood pressure. a leading cause of death. The American Diabetes Association recommends that insulin-dependent type 1 diabetics selfmonitor blood glucose 3–4 times daily. accurate. neurological disorders risk and other health related complications without diligent monitoring blood glucose concentrations. the concentration of fasting plasma glucose is in the range 6. Requirements of a sensor for in vivo glucose monitoring include miniaturization of the device. minimally invasive devices that measure interstitial glucose levels in subcutaneous fat (Cengiz & Tamborlane. 1962) and after that a great number of different glucose biosensors were developed. stroke. Diabetes is a syndrome of disordered metabolism resulting in abnormally high blood sugar levels. Several methods for glucose analysis have been reported.1 Glucose as diabetes biomarker About 3% of the population worldwide suffers from diabetes. calibration error. Biosensors for diabetes applications 3. and its incidence is growing fast. 2009). 1993). Under normal physiological condition. and delay of the interstitial sensor value behind the blood value are still present (Castle & Ward. frequent self-monitoring of glucose concentrations is difficult. convenience to the user and biocompatibility. 3. given the time.com . 1985. Optimal management of diabetes involves patients measuring and recording their own blood glucose levels. while insulin-dependent type 2 diabetics monitor once-daily (American. Therefore it is necessary to develop a simple.Biosensors for Health Applications 75 3. Most sensors are reasonably accurate although sensor error including drift. besides other conditions. long-term stability. most of these methods involve complex procedures or are expensive in terms of costs. Through patient education. Glucose sensors are now widely available as small. blindness. 2010). Glucose biosensor was the first reported biosensor (Clark & Lyons. regular examinations and tighter blood glucose monitoring.9 mmolL−1. as it is the main diabetes biomarker.2 Biosensors for glucose measuring Glucose can be monitored by invasive and non-invasive technologies. The current invasive glucose monitors commercially available use glucose oxidase-based electrochemical methods and the electrochemical sensors are inserted into the interstitial fluid space. microdialysis or ultrafiltration technology has been coupled with glucose biosensors. many of these complications can be reduced significantly (Turner & Pickup. both subcutaneously and intravascular. Long-term biocompatibility has been the main requirement and has limited the use of in vivo glucose sensors. so the variation of the blood glucose level can indicate diabetes mellitus. Diabetic individuals are at a greater heart disease. However. This type of biosensor has been used widely throughout the world for glucose testing in the home bringing diagnosis to on site analysis.1–6.

poor selectivity. Beauharnois et al.1 Cardiovascular disease biomarkers Cardiovascular diseases are highly preventable. The desire to create an artificial pancreas drives for continued research efforts in the biosensor area. Despite the relative ease of use. optical sensors. 1995. which is produced predominantly by macrophages as well as adipocytes. speed and minimal risk of infection involved with infrared spectroscopy. Arya et al. sonophoresis and iontophoresis. Nevertheless. increased concentration of cholesterol in blood (Franco et al. is one of the plasma proteins known as acute-phase proteins and its levels rise dramatically during inflammatory processes occurring in the body.e. One of the most important reasons of the increasing incidences of cardiovascular diseases and cardiac arrest is hypercholesterolemia. Zhou et al. Environment and Biosecurity Non-invasive glucose sensing is the ultimate goal of glucose monitoring and the main approaches being pursued for glucose sensor development are: near infrared spectroscopy.. and useful for therapeutic decision making. In the fabrication of cholesterol biosensor for the estimation of free cholesterol and total cholesterol. 4. yet they are major cause of death of humans over the world. a variety of optical transducers have been employed for cholesterol sensing. growth differentiation factor 15 and Creactive protein (CRP). 2006. 2). 2011).76 Biosensors for Health. i. CRP can rise as high as 1000-fold with inflammation. the drawbacks of in vivo biosensors must be solved before such an insulin modulating system can be achieved. 4. Biosensors for cardiovascular diseases applications 4. This increment is due to a rise in the plasma concentration of IL-6. Problems surrounding direct glucose analysis through excreted physiological fluids include a weak correlation between excreted fluids and blood glucose concentrations. namely monitoring: luminescence. excreted physiological fluid (tears. and difficulties with miniaturization. 2007).. easily detected.. CRP. 2006. www. Determination of the level of other non-myocardial tissue-specific markers might also be helpful. saliva) analysis. enzyme electrodes.. copeptin. Biomarkers have become increasingly important in this setting to supplement electrocardiographic findings and patient history because one or both can be misleading. Singh et al. which reflects different aspects of the development of atherosclerosis or acute ischemia. Electrochemical transducers have been effectively utilized for the estimation of cholesterol in the system (Charpentier & Murr. this technique is hindered by the low sensitivity. The early evaluation of patients with symptoms that indicates an acute coronary syndrome is of great clinical relevance. mainly cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) have been employed as the sensing elements (Arya et al... urine. 2008) (Fig. 2006. Exercise and diet that alter glucose concentrations in the fluids also produce inaccurate results (Pickup et al. frequently required calibrations.2 Biosensors in cardiovascular disease Biosensors for cholesterol measurement comprise the majority of the published articles in the field of cardiovascular diseases. 2005).intechopen.. Cardiac troponin is the only marker used routinely nowadays in this setting because it is specific from the myocardial tissue. 2007. Hence estimation of cholesterol level in blood is important in clinical applications. CRP was found to be the only marker of inflammation that independently predicts the risk of a heart attack. both of which extract glucose from the skin (Koschwanez & Reichert.. Based on number and reliability of optical methods. such as myeloperoxidase. microcalorimetry. Chu et al.com . sweat. 2011).

Zhou et al. such as enzyme stabilization. especially for the patients suffering the heart attack. 2008).. A better comprehension of the bioreagents immobilization and technological advances in the microelectronics are likely to speed up commercialization of the much needed biosensors for cardiovascular diseases.com . 2008.. 2010). 2008. only a few have been successfully launched in the market. electrochemical and acoustic transducers besides approaches to simultaneous analytes measurement (Albrecht et al.. a protein marker for a higher risk of acute myocardial infarction. 2010a. 2010. Other cardiovascular disease biomarkers are also quantified. McBride & Cooper. Pathway of cholesterol oxidase enzyme reaction (Arya et al. quality control and instrumentation design.Biosensors for Health Applications 77 change in color of dye. Qureshi et al. The efforts directed toward the development of cardiovascular disease biosensors have resulted in the commercialization of a few cholesterol biosensors.b. 2010. (2009) used an assay based on virus nanoparticles for troponin I highly sensitive and selective diagnostic.. Sheu et al.. 2008. www. Accurate and fast quantification of cardiac muscle specific biomarkers in the blood enables accurate diagnosis and prognosis and timely treatment of the patients. However. 2008).. It is apparent that increasing incidences of cardiovascular diseases and cardiac arrest in contemporary society denote the necessity of the availability of cholesterol and other biomarkers biosensors. One of the reasons lays in the optimization of critical parameters. Niotis et al. fluorescence and others (Arya et al. CRP measurement rely mainly on immunosensing technologies with optical.. 2. (2010) incorporated streptavidin polystyrene microspheres to the electrode surface of SPEs in order to increase the analytical response of the cardiac troponin T and Park et al.. Silva et al.intechopen. Early and accurate diagnosis of cardiovascular disease is crucial to save many lives. Heyduk et al. Fig.

Furthermore. can be so variable and overlapping that it is difficult to select a specific change or marker for the diagnosis of specific cancers.78 Biosensors for Health. radiation. Pantel & Brakenhoff. as well within tumors from the same location. Therefore. Environment and Biosecurity 5. physical and biological factors such as the exposure to carcinogenic chemicals. The multi-factorial changes (genetic and epigenetic) can cause the onset of the disease and the formation of cancer cells. tissue removal can miss cancer cells at the early onset of the disease.intechopen. 2010). www. 2010).2 Biosensors in cancer disease Existing methods of screening for cancer are heavily based on cell morphology using staining and microscopy which are invasive techniques. including genes and proteins. a range of biomarkers can potentially be analyzed for disease diagnosis.g. Cancer can be caused by a range of factors. in the tumors from different locations (organ). but a set of them that brings difficulties to the correct disease diagnosis.. since it is faster. oncogenes and other modified molecules. These methods should provide information to assist clinicians in making successful treatment decisions and increasing patient survival rate (Tothill. viral infections (e. However. Several biomarkers are current being studied.g. hormones and related molecules. Several cancer biomarkers are listed in Table 1. Breast cancer is now also the leading cause of cancer death among females in economically developing countries. both presence and concentration level. Biosensor-based detection becomes practical and advantageous for cancer clinical testing. both genetic and environmental. The development of protein based biomarkers for biosensors use in cancer diagnosis is more attractive than genetic markers due to protein abundance.1 Cancer biomarkers Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. proteins (enzymes and glycoproteins). Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females and lung cancer is the leading cancer site in males. urine and others is one of the methods applied in the detection of the disease. clinical testing is also very complex. stomach cancer). A range of biomarkers have been identified with different types of cancers. more user-friendly. RNA.. recovery and cost effective technique for the development of point-of-care devices (Li et al. Biosensors for cancer applications 5. As the causes of cancer are so diverse. a shift from the previous decade during which the most common cause of cancer death was cervical cancer (Jemal et al. Chemical. These include DNA modifications. 2009).com . 2004).. The analysis of biomarkers in body fluids such as blood. particularly smoking. however few of them have routine cancer clinical testing importance because of their complexity. 2010).. molecules of the immune system. Solid cancers are a leading cause of morbidity and mortality worldwide. This disease continues to increase globally largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors. bacterial (e. e. cervical cancer) and toxins (aflatoxin. These biomarkers or molecular signatures can be produced either by the tumor itself or by the body in response to the presence of cancer (Robert. 2011). All the changes which take place. primarily due to the failure of effective clinical detection and treatment of metastatic disease in distant sites (Chambers et al. 2002. no single gene is universally altered during this process. can be essential for the diagnosis of early disease onset. 5.g. liver cancer) can lead to cancer development (Vineis et al. Multi-marker profiles.

CA125. CYFRA21-1.. HER2. p53.. FAP. CA19-9. VEGF. CEA NY-ESO-1. Bcl-2. NSE Tyrosinase. The drawbacks include that monoclonal antibodies are more difficult to maintain and can be more expensive than polyclonal antibodies (Huang et al. SCC-Ag. CA19-9. Antibodies (monoclonal and polyclonal) have been applied in cancer diagnostics tests targeting cancer cells and biomarkers. applying these molecules in sensors has been successful. SCC. 2010).PR. CA27. CEA. CA19-9 Breast Bladder Cervix Colon Esophagus Leukemia Liver Lung Melanoma Ovarian Pancreas Prostate Solid tumors Stomach Table 1.Biosensors for Health Applications 79 less expensive and less technically demanding than microarray or proteomic analyses. Khati. The use of monoclonal antibodies however. CYFRA 21-1 P53. BLCA-4. significant technical development is still needed. CEA.. MIC-1 PSA. being antibodies the most widely used.29. Those molecules can be synthesized after a selection from combinatorial libraries with higher specificity and sensitivity when compared to the antibody molecule. CA15-3. TPA. Cancer biomaker www. MUC-1. The advantages of using these molecules are that they are robust. CEA. NY-ESO-1 CA125. phage display peptides. 2009. A range of molecular recognition molecules have been used for biomarker detection. HA-Hase. Polyclonal antibodies can be raised against any biomarker or cells and with the introduction of high throughput techniques. hCG. results in more specific tests.com . PAP Circulating tumour cells in biological fluids. CA24-2. less expensive to produce and can be modified easily to aid immobilization on the sensor surface as well as adding labels as the maker for detection (Liu et al. CYFRA 21-1. aptamers. Brn-3a. CEA. binding proteins and synthetic peptides as well as metal oxides materials have been fabricated as affinity materials and used for analyte detection and analysis (Sadik et al. M-CSF HNPCC. Replacing natural biomolecules with artificial receptors or biomimics has therefore become an attractive area of research in recent years. p53 SCC Chromosomal aberrations AFP. expression of targeted growth factor receptors CA72-4. FDP. CEA BRCA1. 2010). ER. For cancer diagnosis multi-array sensors would be beneficial for multi-marker analysis. synthetic (artificial) molecular recognition elements such as nanomaterials. 2007). AFP.intechopen. NY-BR-1. more stable. BRCA2. particularly for protein based biosensors. More recently. CEA. ING1 BAT. NMP22. MCM. However. CEA CA19-9.

2009b). 2008). Santa Clara. advanced manufacturing techniques and cost reduction (Rasooly & Jacobson. development of multi-channel biosensors. Environment and Biosecurity For cancer biomarkers analysis. the instruments used for signal readout are usually expensive and are more suitable for laboratory settings. device miniaturization and integration. 2006). but much attention in recent years has been devoted to impedance based transducers since they are classified as label-free detection sensors.80 Biosensors for Health. In this type of device a single stranded DNA sequence is immobilized on the electrode surface where DNA hybridization takes place (Ahmed. Biosensors can fulfill these requirements. Biosensors for measurement of blood metabolites such as glucose. 2006). Electrochemical affinity sensors based on antibodies offer great selectivity and sensitivity for early cancer diagnosis and these include amperometric. Recently. microcantilever based sensors have also been applied for early-stage diagnosis of hepatocellular carcinoma (Liu et al. bioaffinity based electrochemical biosensors are usually applied to detect gene mutations of biomarkers and protein biomarkers. for example. However. using both electrochemical and optical modes of transduction. 2011). Other biosensor platforms such as grating couplers. electrochemical devices have been developed based on DNA hybridization and used for cancer gene mutation detection. multiplex analysis of several biomarkers where arrays of sensors need to be developed on the same chip. conveniently and frequently for efficient cancer treatment (Chung et al. biosensor devices need to be further developed and improved to face these new challenges to allow. Besides based on antibodies. advances in sample preparation. lactate. However. Many commercially available platforms use fluorescence labels as the detection system.. In this method the antibody (or antigen) is labeled with an enzyme such as horseradish peroxidase (HRP). Conclusion A precise diagnostic for a disease is essential for a successful treatment and recovery of patients suffering from it. the point-of-care testing is not yet available. microfluidics integration. or alkaline phosphatase (AP) and these will then catalyze an added substrate to produce an electroactive species which can then be detected on an electrochemical transducer. In spite of the achieved development in cancer biosensing. sensitive and able to detect multiple biomarkers that exist at low concentrations in biological fluids.intechopen. are commercially developed and used www. Wang. 6. Electrochemical detection of rare circulating tumor cells has the potential to provide clinicians with a standalone system to detect and monitor changes in cell numbers throughout therapy. Diagnostics methods must be simple. 2009). However. such as CEA. Biosensors are firmly established for application in clinical chemical analysis. 2005. urea and creatinine. much of the technology is still at the research stage (Lin & Ju.. As an example the Affymetrix gene chip (Affymetrix Inc. improvement in recognition ligands. USA) can be used for screening cancer and cancer gene identification. Amperometric and potentiometric transducers have been the most commonly used.. development of more sensitive transducers. potentiometric and impedimetric/conductivity devices. Different SPR based biosensors have been developed for cancer markers detection based on the above optical systems (Tothill. ELISA based assays conducted on the electrode surface are the most frequently used techniques for cancer protein markers analysis. These are classified as labelfree and real-time affinity reaction detection systems. In order to achieve this goal challenges must be overcome such as: development of reproducible biomarker assays. resonant mirrors and surface plasmon based systems have also been used for cancer biomarkers diagnosis.com .

few biosensors have been developed for cardiovascular and cancer-related clinical testing. DNA chips are being incorporated into total analysis systems. improving the signal produced by the biochemical reaction or increasing the sensitivity of the transducer while reducing background noise. and improvements in this area may ultimately be limited by resolution of the detection transducer. A clear direction for future work in biosensor research is in molecular diagnostics. Further development and improvement of nanotechnologies will be needed to produce nanoscale devices. based on genetic and epigenetic signatures. both genomic and proteomic. including microfluidics and the biosensor on a single structure. While immunosensors have difficulty competing with traditional immunoassay based mainly on sensitivity requirements. enable multitarget analyses and automation and reduced costs of diagnostic testing. Cancer biomarkers identified from basic and clinical research. in the future. The use of biosensors for cancer clinical testing may increase assay speed and flexibility. These systems should include. 2006).com . Some recent examples of transduction modes with enhanced sensitivity include microcantilevers for the detection of mass changes upon detection of a binding event and quartz crystal microbalances capable of monitoring formation and rupturing of chemical bonds by sensing acoustic emissions. Ligands and probes for these markers can then be combined with detectors to produce biosensors for cancer-related clinical testing. with expanded sizes of arrays using reduced sample volume. Biosensors have the potential to deliver molecular testing to the community health care setting and to underserved populations. Central to development of lab-on-a-chip analysis system will be the homogeneous sensing formats and microfabrication technologies for DNA analysis. The future of such devices for rapid determination of a disease could be especially www. for selftesting. a user-friendly handling system. chemical analysis and signal acquisition capabilities. Development of molecular tools. as well as continued development of sample preparation methods and multi-channel biosensors able to analyze many cancer markers simultaneously. allowing monitoring of hybridization in real time without the need for separation steps. in the case of glucose. One recent step towards a homogeneous assay has been the development of synthetic polymeric probes that emit fluorescence only after the hybridization to native DNA targets. Ultrasensitive transducer technologies will be required. Point-of-care cancer testing requires integration and automation of the technology as well as development of appropriate sample preparation methods (Rasooly & Jacobson. they hold promise for testing where some sensitivity can be sacrificed for improved ease of use and faster time to result. in point-of-care settings and.intechopen. such as in near-patient testing for cardiac and cancer markers. changes in gene expression and protein profiles and protein posttranslational modifications has opened new opportunities for utilizing biosensors in cancer testing. to profile tumors and produce molecular signatures. Although biosensors are used for several clinical applications. This goal will require enhancing the signal-to-noise rate. The latter has demonstrated sensitivity to detect a single virus particle. Harnessing the potential of biosensors is challenging because of cancer’s complexity and diversity. Improving the sensitivity of DNA biosensors for a single-molecule detection in an unamplified sample is an important goal to achieve. Successful development of biosensor-based cancer testing will require continued development and validation of biomarkers and development of ligands for those biomarkers. and from genomic and proteomic analyses must be validated. Increasing the arrays amplitude for more complete and rapid DNA sequencing information is another area of focus.Biosensors for Health Applications 81 routinely in the laboratory. no need for sample preparation.

Vol. Environment and Biosecurity used for point-of-care application. No. miniaturization.5. BD. The future is very bright for biosensors. and system integration with high throughput for multiple tasks. Future innovation in biosensor technology to include biomarkers patterns. Clinical practice recommendations 1997 Introduction. The concept of using nanomaterials in the development of sensors for biomarkers diagnosis will make these devices highly sensitive and more applicable for point-of-care early diagnosis.intechopen. however.391. thick and thin film physics.. Analytical chemistry has changed considerably. pp. C. software and microfluidics can make these devices of high potential for health applications. Homogeneous assay formats. require a concerted multi-disciplinary approach for the sensor systems to successfully make the very big jump from the research and development laboratory to the market place. Diabetes Care. References Ahmed. (2008). M. S1–S70. Mining the oncoproteome and studying molecular interactions for biomarker development by 2DE. (2008). for example. (1997). Kaeppel. No. Such requirements pose a great challenge in biosensor technology which is often designed to detect one single or a few target analytes.. to improve biocomponent stability. (2008). Arya.23. driven by automation. 1845-1852. molecular biology. pp. Molecular biology will play a central role in the future of biosensor development. Datta. Early diagnosis will aid in the increase in the survival rate of patients and successful development of biosensors for disease diagnosis and monitoring will require appropriate funding to move the technology from research through to the realization of commercial products. pp. 7.82 Biosensors for Health. G. No. pp. Successful biosensors must be versatile to support interchangeable biorecognition elements. N. & Gauglitz. 2003). ChIP and SPR technologies. Albrecht. 1083-1100. biochemistry. However. These advancements will.7.3. Expert Review of Proteomics. & Malhotra. Vol. removing the need for sample preparation and amplification steps and mass fabrication will be important to lowering cost. and for the development of aptamers. FE. SK. and in addition miniaturization must be feasible to allow automation for parallel sensing with ease of operation at a competitive cost. materials science and electronics with the necessary expertise has revealed the promise for development of viable clinical useful biosensor. Vol. Biosensor research and development over the past decades have demonstrated that it is still a relatively young technology. Analytical and Bioanalytical Chemistry. 469-496. American diabetes association. Biosensors and Bioelectronics. Recent advances in cholesterol biosensor. Combination of several new techniques.20.com . cost and quality control of these devices must be strictly adjusted for the accurate devices to gain popular acceptance.5. Vol. No. derived from physical chemistry. Two immunoassay formats for fully automated CRP detection in human serum. Suppl 1. The highly reproducible synthetic approach and ease of immobilization of aptamers hold great promise for the custom design of future biosensors for molecular diagnostics (D’Orazio. Many of the more recent major advances had to await miniaturization technologies that are just becoming available through research in the electronic and optical solid state circuit industries. www. The rationale behind the slow and limited technology transfer could be attributed to cost considerations and some key technical barriers.

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Hotel Equatorial Shanghai No. 2011 A biosensor is a detecting device that combines a transducer with a biologically sensitive and selective component. China Phone: +86-21-62489820 Fax: +86-21-62489821 . July.intechopen. Shanghai. Environment and Biosecurity. Biosensors for Health and Biosensors for Environment and Biosecurity. InTech. Biosensors for health applications. The book consists of 24 chapters written by 76 authors and divided in three sections: Biosensors Technology and Materials. Prof. ISBN: 978-953-307-443-6.com InTech China Unit 405.intechopen. This book covers a wide range of aspects and issues related to biosensor technology. How to reference In order to correctly reference this scholarly work. Yan An Road (West). food and human body at low cost if compared with traditional analytical techniques.Biosensors for Health. 200040. Biosensors can measure compounds present in the environment. Croatia Phone: +385 (51) 770 447 Fax: +385 (51) 686 166 www. Environment and Biosecurity Edited by Prof. Biosensors for Health. Pier Andrea Serra ISBN 978-953-307-443-6 Hard cover. 2011 Published in print edition July.). Pier Andrea Serra (Ed. chemical processes. feel free to copy and paste the following: Cibele Gouvea (2011). bringing together researchers from 16 different countries.65. Office Block. 540 pages Publisher InTech Published online 19. Available from: http://www.com/books/biosensors-for-health-environment-and-biosecurity/biosensors-for-healthapplications InTech Europe University Campus STeP Ri Slavka Krautzeka 83/A 51000 Rijeka.